chr1-205791624-G-A

Position:

• chr1-205791624-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_173854.6(SLC41A1):​c.1451C>T​(p.Ala484Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC41A1 NM_173854.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.99

Genes affected

SLC41A1 (HGNC:19429): (solute carrier family 41 member 1) Enables magnesium ion transmembrane transporter activity and magnesium:sodium antiporter activity. Involved in cellular magnesium ion homeostasis; cellular response to magnesium ion; and magnesium ion transmembrane transport. Located in basolateral plasma membrane. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.903

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC41A1	NM_173854.6	c.1451C>T	p.Ala484Val	missense_variant	11/11	ENST00000367137.4
SLC41A1	XM_047416887.1	c.1451C>T	p.Ala484Val	missense_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC41A1	ENST00000367137.4	c.1451C>T	p.Ala484Val	missense_variant	11/11	1	NM_173854.6	P1
SLC41A1	ENST00000468057.5	n.1247C>T		non_coding_transcript_exon_variant	10/10	2
SLC41A1	ENST00000484228.1	n.1517C>T		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 02, 2024

The c.1451C>T (p.A484V) alteration is located in exon 11 (coding exon 10) of the SLC41A1 gene. This alteration results from a C to T substitution at nucleotide position 1451, causing the alanine (A) at amino acid position 484 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Pathogenic	33
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.58	D
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.99
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.041	D
MetaRNN	Pathogenic	0.90	D
MetaSVM	Benign	-0.40	T
MutationAssessor	Pathogenic	3.2	M
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.88	D
PROVEAN	Uncertain	-3.5	D
REVEL	Uncertain	0.62
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.95
MutPred		0.74		Loss of helix (P = 0.079);
MVP		0.20
MPC		1.4
ClinPred		0.99	D
GERP RS		5.8
Varity_R		0.69
gMVP		0.98

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-205760752;